Long-term natural history and patterns of sporadic vestibular schwannoma growth: A multi-institutional volumetric analysis of 952 patients

Abstract

Background The current study aims to characterize the natural history of sporadic vestibular schwannoma volumetric tumor growth, including long-term growth patterns following initial detection of growth. Methods Volumetric tumor measurements from 3,505 serial MRI studies were analyzed from unselected consecutive patients undergoing wait-and-scan management at three tertiary referral centers between 1998 and 2018. Volumetric tumor growth was defined as a change in volume ≥20%. Results Among 952 patients undergoing observation, 622 experienced tumor growth with initial growth-free survival rates (95% CI) at 1, 3, and 5 years following diagnosis of 66% (63-69), 30% (27-34), and 20% (17-24). Among 405 patients who continued to be observed despite demonstrating initial growth, 210 experienced subsequent tumor growth with subsequent growth-free survival rates at 1, 3, and 5 years following initial growth of 77% (72-81), 37% (31-43), and 24% (18-31). Larger tumor volume at initial growth (HR 1.13, p=0.02) and increasing tumor growth rate (HR 1.31; p<0.001) were significantly associated with an increased likelihood of subsequent growth, whereas a longer duration of time between diagnosis and detection of initial growth was protective (HR 0.69; p<0.001). Conclusions While most vestibular schwannomas exhibit an overall propensity for volumetric growth following diagnosis, prior tumor growth does not perfectly predict future growth. Tumors can subsequently grow faster, slower, or demonstrate quiescence and stability. Larger tumor size and increasing tumor growth rate portend a higher likelihood of continued growth. These findings can inform timing of intervention: whether upfront at initial diagnosis, after detection of initial growth, or only after continued growth is observed.

Spontaneous Volumetric Tumor Regression During Wait-and-Scan Management of 952 Sporadic Vestibular Schwannomas

“…These reliability measurements parallel previous published data (20). Lastly, we previously reported that the clinical features across the three institutions were similar (12). For these reasons, we believe that the methodology used in the current study is valid.…”

“…Therefore, rather than embarking on observation to "see if the tumor grows," it should instead be assumed at the outset of wait-and-scan management that all vestibular schwannomas grow during a patient's lifetime. This claim can be intuited by appealing to the sporadic development of these tumors (i.e., people are not born with sporadic vestibular schwannomas, and each tumor must have grown to the size it is at the time of detection), and the claim is further supported by the recognition that most (80%) tumors show some degree of growth during extended MRI surveillance (12). Taken together, when pursuing wait-and-scan management in sporadic vestibular schwannoma, rather than reflexively treating all patients who demonstrate tumor growth, detection of tumor growth must only represent one factor among many that influences the decision to pursue definitive treatment, recognizing that the likelihood of future growth depends on factors such as the magnitude of previous growth and the recognition that small changes in tumor size bear little impact on patient outcomes during treatment (12,18).…”

“…This claim can be intuited by appealing to the sporadic development of these tumors (i.e., people are not born with sporadic vestibular schwannomas, and each tumor must have grown to the size it is at the time of detection), and the claim is further supported by the recognition that most (80%) tumors show some degree of growth during extended MRI surveillance (12). Taken together, when pursuing wait-and-scan management in sporadic vestibular schwannoma, rather than reflexively treating all patients who demonstrate tumor growth, detection of tumor growth must only represent one factor among many that influences the decision to pursue definitive treatment, recognizing that the likelihood of future growth depends on factors such as the magnitude of previous growth and the recognition that small changes in tumor size bear little impact on patient outcomes during treatment (12,18). Especially in light of the comparable quality of life and cost-effectiveness evidence supporting observation, continued observation is particularly justifiable in older patients with small tumors and non-useful hearing.…”

“…An exhaustive discussion of the limitations surrounding the cohort presently studied is described elsewhere (12). When interpreting the particular results of the current work, it is also important to remember that patients are being continually censored-because of tumor growth leading to treatment, treatment for other reasons, loss to follow-up, or death-throughout the survival analysis.…”

“…Multiple recent large volumetric analyses demonstrate that the growth capacity of sporadic vestibular schwannomas is often significantly underestimated by traditional natural history studies using linear tumor measurements (8)(9)(10)(11). To this end, large volumetric data show that approximately 80% of tumors will be found to demonstrate growth with sufficient follow-up during observation (12). Presumably, this heightened sensitivity of volumetric tumor measurements to detect tumor growth applies in the opposite direction-to detect shrinking tumor volumes-as well.…”